Pathophysiology of Congenital Nephrotic Syndrome of the Finnish type

Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal recessive disease which is highly enriched in the Finnish population. It is caused by mutations in the NPHS1 gene encoding for nephrin, which is a major component of the glomerular filtration barrier in the kidney. Patients with NPHS1 have heavy proteinuria and nephrotic syndrome (NS) from birth and develop renal fibrosis in early childhood. Renal transplantation (TX) is the only curative treatment for NPHS1. These patients form the largest group of pediatric kidney transplant children in our country. The NPHS1 kidneys are removed in infancy and they serve as an excellent human material for studies of the pathophysiology of proteinuric kidney diseases. Sustained proteinuria is a major factor leading to end-stage renal failure and understanding this process is crucial for nephrology. In this study we investigated the glomerular and tubulointerstitial changes that occur in the NPHS1 kidneys during infancy as well as the expression of nephrin in non-renal tissues. We also studied the pathology and management of recurrent proteinuria in kidney grafts transplanted to NPHS1 children. Severe renal lesions evolved in patients with NPHS1 during the first months of life. Glomerular sclerosis developed through progressive mesangial sclerosis, and capillary obliteration was an early consequence of this process. Shrinkage of the glomerular tuft was common, whereas occlusion of tubular opening or protrusion of the glomerular tuft into subepithelial space or through the Bowman's capsule were not detected. Few inflammatory cells were detected in the mesangial area. The glomerular epithelial cells (podocytes) showed severe ultrastructural changes and hypertrophy. Podocyte proliferation and apoptosis were rare, but moderate amounts of podocytes were detached and ended up in the urine. The results showed that endocapillary lesions not extracapillary lesions, as generally believed were important for the sclerotic process in the NPHS1 glomeruli. In the tubulointerstitium, severe lesions developed in NPHS1 kidneys during infancy. Despite heavy proteinuria, tubular epithelial cells (TECs) did not show transition into myofibroblasts. The most abundant chemokines in NPHS1 tissue were neutrophil activating protein-2 (NAP-2), macrophage inhibiting factor (MIF), and monocyte chemoattractant protein-1 (MCP-1). Interstitial inflammation and fibrosis were first detected in the paraglomerular areas and the most abundant inflammatory cells were monocytes/macrophages. Arteries and arterioles showed intimal hypertrophy, but the pericapillary microvasculature remained quite normal. However, excessive oxidative stress was evident in NPHS1 kidneys. The results indicated that TECs were relatively resistant to the heavy tubular protein load. Nephrin was at first thought to be podocyte specific, but some studies especially in experimental animals have suggested that nephrin might also be expressed in non-renal tissues such as pancreas and central nervous system. The knowledge of nephrin biology is important for the evaluation of nephrin related diseases. In our study, no significant amounts of nephrin protein or mRNA were detected in non-renal tissues of man and pig as studied by immunohistochemistry and in situ hybridization. The phenotype analysis of NPHS1 children, who totally lack nephrin, revealed no marked impairment in the neurological, testicular, or pancreatic function speaking against the idea that nephrin would play an important functional role outside the kidney. The NPHS1 kidneys do not express nephrin and antibodies against this major glomerular filter protein have been observed in NPHS1 children after renal TX most likely as an immune reaction against a novel antigen. These antibodies have been associated with the development of recurrent NS in the kidney graft of NPHS1 patients. In our study, a third of the NPHS1 patients homozygous for Fin-Major mutation developed recurrent NS in the transplanted graft. Re-transplantations were performed to patients who lost their graft due to recurrent NS and heavy proteinuria immediately developed in all cases. While 73% of the patients had detectable serum anti-nephrin antibodies, the kidney biopsy findings were minimal. Introduction of plasma exchange (PE) to the treatment of recurrent nephroses increased the remission rate from 54% to 89%. If remission was achieved, recurrent NS did not significantly deteriorate the long term graft function. In conclusion, the results show that the lack of nephrin in podocyte slit diaphragm in NPHS1 kidneys induces progressive mesangial expansion and glomerular capillary obliteration and inflicts interstitial fibrosis, inflammation, and oxidative stress with surprisingly little involvement of the TECs in this process. Nephrin appears to have no clinical significance outside the kidney. Development of antibodies against nephrin seems to be a major cause of recurrent NS in kidney grafts of NPHS1 patients and combined use of PE and cyclophosphamide markedly improved remission rates.

Place making for knowledge generation and innovation: Planning and branding Brisbane’s knowledge community precincts

Knowledge generation and innovation have been a priority for global city administrators particularly during the last couple of decades. This is mainly due to the growing consensus in identifying knowledge-based urban development as a panacea to the burgeoning economic problems. Place making has become a critical element for success in knowledge-based urban development as planning and branding places is claimed to be an effective marketing tool for attracting investment and talent. This paper aims to investigate the role of planning and branding in place making by assessing the effectiveness of planning and branding strategies in the development of knowledge and innovation milieus. The methodology of the study comprises reviewing the literature thoroughly, developing an analysis framework, and utilizing this framework in analyzing Brisbane’s knowledge community precincts—namely Boggo Road Knowledge Precinct, Kelvin Grove Urban Knowledge Village, and Sippy Downs Knowledge Town. The analysis findings generate invaluable insights in Brisbane’s journey in place making for knowledge and innovation milieus and communities. The results suggest as much as good planning, branding strategies and practice, the requirements of external and internal conditions also need to be met for successful place making in knowledge community precincts.

Understanding the Knowledge Needs of Designers During Design Process in Industry

Product success is substantially influenced by satisfaction of knowledge needs of designers, and many tools and methods have been proposed to support these needs. However, adoption of these methods in industry is minimal. This may be due to an inadequate understanding of the knowledge needs of designers in industry. This research attempts to develop a better understanding of these needs by undertaking descriptive studies in an industry. We propose a taxonomy of knowledge, and evaluate this by analyzing the questions asked by the designers involved in the study during their interactions. Using the taxonomy, we converted the questions asked into a generic form. The generic questions provide an understanding about what knowledge must be captured during design, and what its structure should be.

Reforming technology company incentive programs for achieving knowledge-based economic development:a Brazil-Australia comparative study

This doctoral thesis aims to demonstrate the importance of incentives to technology-based firms as a strategy to promote knowledge-based economic development (KBED). To remain competitive, technology-based firms must innovate and seek new markets; therefore, this study aims to propose an incentive model to technology-based firms as a strategy to promote knowledge-based urban development, according to framework described by Yigitcanlar (2011). This is an exploratory and descriptive research with a qualitative approach. Surveys were carried out with national trade associations that represented technology-based firms both in Brazil and Australia. After analysing the surveys, structured interviews were conducted with government representatives, trade associations and businessmen who had used financial support by the federal government. When comparing both countries, the study found the importance of direct incentives through tax incentives, for it is a less bureaucratic, quicker and more direct process for firms. We suggest to include the terms incentives in the framework of knowledge-based urban development, as one of the pillars that contribute to knowledge-based economic development.

Futility and the law: Knowledge, practice and attitudes of doctors in end of life care

Despite the potential harm to patients (and others) and the financial cost of providing futile treatment at the end of life, this practice occurs. This article reports on empirical research undertaken in Queensland that explores doctors’ perceptions about the law that governs futile treatment at the end of life, and the role it plays in medical practice. The findings reveal that doctors have poor knowledge of their legal obligations and powers when making decisions about withholding or withdrawing futile treatment at the end of life; their attitudes towards the law were largely negative; and the law affected their clinical practice and had or would cause them to provide futile treatment.

Consent Practices and Biomedical Knowledge Production in Tissue Economies

The use of human tissue sample collections has become an important tool in biomedical research. The collection, use and distribution of human tissue samples, which include blood and diagnostic tissue samples, from which DNA can be extracted and analyzed has also become a major bio-political preoccupation, not only in national contexts, but also at the transnational level. The foundation of medical research rests on the relationship between the doctor and the research subject. This relationship is a social one, in that it is based on informed consent, privacy and autonomy, where research subjects are made aware of what they are getting involved in and are then able to make an informed decision as to whether or not to participate. Within the post-genomic era, however, our understanding of what constitutes informed consent, privacy and autonomy is changing in relation to the needs of researchers, but also as a reflection of policy aspirations. This reflects a change in the power relations between the rights of the individual in relation to the interests of science and society. Using the notions of tissue economies and biovalue (Waldby, 2002) this research explores the changing relationship between sources and users of samples in biomedical research by examining the contexts under which human tissue samples and the information that is extracted from them are acquired, circulated and exchanged in Finland. The research examines how individual rights, particularly informed consent, are being configured in relation to the production of scientific knowledge in tissue economies in Finland from the 1990s to the present. The research examines the production of biovalue through the organization of scientific knowledge production by examining the policy context of knowledge production as well as three case studies (Tampere Research Tissue Bank, Hereditary Non-polyposis Colorectal Cancer and the Finnish Genome Information Center) in which tissues are acquired, circulated and exchanged in Finland. The research shows how interpretations of informed consent have become divergent and the elements and processes that have contributed to these differences. This inquiry shows how the relationship between the interests of individuals is re-configured in relation to the interests of science and society. It indicates how the boundary between interpretations of informed consent, on the one hand, and social and scientific interests, on the other, are being re-drawn and that this process is underscored, in part, by the economic, commercial and preventive potential that research using tissue samples are believed to produce. This can be said to fundamentally challenge the western notion that the rights of the individual are absolute and inalienable within biomedical legislation.

Knowledge through Discussion : An Interpretation of Epistemology in Plato's Meno

According to Meno s paradox we cannot inquire into what we do not know because we do not know what we are inquiring into. There are many ways to interpret the paradox but the central issue about our ability to reach truth is a profound one. In the dialogue Meno, Plato presents the paradox and an outline of a solution which enables us to reach knowledge (epistēmē) through philosophical discussion. During the last century Meno has often been considered transitional between Socratic thinking and Plato s own philosophy, and thus the dialogue has not been adequately interpreted as an integrated whole. Therefore the distinctive epistemology of the dialogue has not gained due notice. In this thesis the dialogue is analysed as an integrated whole and the philosophical interpretation also takes into account its dramatic features. The thesis emphasises the role of language and definitions in acquiring knowledge. Among the results concerning these subjects is a new interpretation of Socrates s defintion of shape (schēma). The theory of anamnēsis all learning is recollection in the Meno is argued to answer the paradox philosophically although Plato s presentation also contains playful and ironic elements. The background of the way Plato presents his case is that he appreciated the fact that no argument can plausibly demonstrate that argumentation is able to reach truth. In the Meno, Plato makes the earliest explicit distinction between knowledge and true belief in the history of Western philosophy. He also gives a definition of knowledge which is the basis of the so called classical definition of knowledge as justified true belief. In the Meno, true beliefs become knowledge when someone ties them down by reasoning about the explanation. The analysis of the epistemology of the dialogue from this perspective gives an interpretation which integrates the central concepts of the epistemology in the dialogue elenchos, anamnēsis and hypothetical inquiry into a unified whole which contains a plausible argument according to which the ignorant can reach knowledge through discussion. The conception that emerges by such an analysis is interesting both from the point of view of current interests and that of the history of philosophy. The method of knowledge acquisition in the Meno can, for example, be seen as a predecessor of modern scientific methods. The Meno is the earliest Greek mathematical text that has survived in its original form. The analysis presented in the thesis of the geometric passages in the dialogue provides new results both concerning Socrates s geometry lesson with the slave and the example presenting the hypothetical method. Concerning the latter, a new interpretation is presented. Keywords: anamnēsis, epistēmē, knowledge, Meno s paradox, Plato

Perspectives on knowledge creating inquiry in higher education

Higher education is faced with the challenge of strengthening students competencies for the constantly evolving technology-mediated practices of knowledge work. The knowledge creation approach to learning (Paavola et al., 2004; Hakkarainen et al., 2004) provides a theoretical tool to address learning and teaching organized around complex problems and the development of shared knowledge objects, such as reports, products, and new practices. As in professional work practices, it appears necessary to design sufficient open-endedness and complexity for students teamwork in order to generate unpredictable and both practically and epistemologically challenging situations. The studies of the thesis examine what kinds of practices are observed when student teams engage in knowledge creating inquiry processes, how the students themselves perceive the process, and how to facilitate inquiry with technology-mediation, tutoring, and pedagogical models. Overall, 20 student teams collaboration processes and productions were investigated in detail. This collaboration took place in teams or small groups of 3-6 students from multiple domain backgrounds. Two pedagogical models were employed to provide heuristic guidance for the inquiry processes: the progressive inquiry model and the distributed project model. Design-based research methodology was employed in combination with case study as the research design. Database materials from the courses virtual learning environment constituted the main body of data, with additional data from students self-reflections and student and teacher interviews. Study I examined the role of technology mediation and tutoring in directing students knowledge production in a progressive inquiry process. The research investigated how the scale of scaffolding related to the nature of knowledge produced and the deepening of the question explanation process. In Study II, the metaskills of knowledge-creating inquiry were explored as a challenge for higher education: metaskills refers to the individual, collective, and object-centered aspects of monitoring collaborative inquiry. Study III examined the design of two courses and how the elaboration of shared objects unfolded based on the two pedagogical models. Study IV examined how the arranged concept-development project for external customers promoted practices of distributed, partially virtual, project work, and how the students coped with the knowledge creation challenge. Overall, important indicators of knowledge creating inquiry were the following: new versions of knowledge objects and artifacts demonstrated a deepening inquiry process; and the various productions were co-created through iterations of negotiations, drafting, and versioning by the team members. Students faced challenges of establishing a collective commitment, devising practices to co-author and advance their reports, dealing with confusion, and managing culturally diverse teams. The progressive inquiry model, together with tutoring and technology, facilitated asking questions, generating explanations, and refocusing lines of inquiry. The involvement of the customers was observed to provide a strong motivation for the teams. On the evidence, providing team-specific guidance, exposing students to models of scientific argumentation and expert work practices, and furnishing templates for the intended products appear to be fruitful ways to enhance inquiry processes. At the institutional level, educators do well to explore ways of developing collaboration with external customers, public organizations or companies, and between educational units in order to enhance educational practices of knowledge creating inquiry.

Future chemistry teachers use of knowledge dimensions and high-order cognitive skills in pre-laboratory concept maps

This poster describes a pilot case study, which aim is to study how future chemistry teachers use knowledge dimensions and high-order cognitive skills (HOCS) in their pre-laboratory concept maps to support chemistry laboratory work. The research data consisted of 168 pre-laboratory concept maps that 29 students constructed as a part of their chemistry laboratory studies. Concept maps were analyzed by using a theory based content analysis through Anderson & Krathwohls' learning taxonomy (2001). This study implicates that novice concept mapper students use all knowledge dimensions and applying, analyzing and evaluating HOCS to support the pre-laboratory work.

The Protection of Traditional Knowledge Associated with Genetic Resources: The Role of Databases and Registers

"The Protection of Traditional Knowledge Associated with Genetic Resources: The Role of Databases and Registers" ABSTRACT Yovana Reyes Tagle The misappropriation of TK has sparked a search for national and international laws to govern the use of indigenous peoples knowledge and protection against its commercial exploitation. There is a widespread perception that biopiracy or illegal access to genetic resources and associated traditional knowledge (TK) continues despite national and regional efforts to address this concern. The purpose of this research is to address the question of how documentation of TK through databases and registers could protect TK, in light of indigenous peoples increasing demands to control their knowledge and benefit from its use. Throughout the international debate over the protection of TK, various options have been brought up and discussed. At its core, the discussion over the legal protection of TK comes down to these issues: 1) The doctrinal question: What is protection of TK? 2) The methodological question: How can protection of TK be achieved? 3) The legal question: What should be protected? And 4) The policy questions: Who has rights and how should they be implemented? What kind of rights should indigenous peoples have over their TK? What are the central concerns the TK databases want to solve? The acceptance of TK databases and registers may bring with it both opportunities and dangers. How can the rights of indigenous peoples over their documented knowledge be assured? Documentation of TK was envisaged as a means to protect TK, but there are concerns about how documented TK can be protected from misappropriation. The methodology used in this research seeks to contribute to the understanding of the protection of TK. The steps taken in this research attempt to describe and to explain a) what has been done to protect TK through databases and registers, b) how this protection is taking place, and c) why the establishment of TK databases can or cannot be useful for the protection of TK. The selected case studies (Peru and Venezuela) seek to illustrate the complexity and multidisciplinary nature of the establishment of TK databases, which entail not only legal but also political, socio-economic and cultural issues. The study offers some conclusions and recommendations that have emerged after reviewing the national experiences, international instruments, work of international organizations, and indigenous peoples perspectives. This thesis concludes that if TK is to be protected from disclosure and unauthorized use, confidential databases are required. Finally, the TK database strategy needs to be strengthened by the legal protection of the TK itself.

Social Media as a Form of Organizational Knowledge Sharing

This study investigates the role of social media as a form of organizational knowledge sharing. Social media is investigated in terms of the Web 2.0 technologies that organizations provide their employees as tools of internal communication. This study is anchored in the theoretical understanding of social media as technologies which enable both knowledge collection and knowledge donation. This study investigates the factors influencing employees’ use of social media in their working environment. The study presents the multidisciplinary research tradition concerning knowledge sharing. Social media is analyzed especially in relation to internal communication and knowledge sharing. Based on previous studies, it is assumed that personal, organizational, and technological factors influence employees’ use of social media in their working environment. The research represents a case study focusing on the employees of the Finnish company Wärtsilä. Wärtsilä represents an eligible case organization for this study given that it puts in use several Web 2.0 tools in its intranet. The research is based on quantitative methods. In total 343 answers were obtained with the aid of an online survey which was available in Wärtsilä’s intranet. The associations between the variables are analyzed with the aid of correlations. Finally, with the aid of multiple linear regression analysis the causality between the assumed factors and the use of social media is tested. The analysis demonstrates that personal, organizational and technological factors influence the respondents’ use of social media. As strong predictive variables emerge the benefits that respondents expect to receive from using social media and respondents’ experience in using Web 2.0 in their private lives. Also organizational factors such as managers’ and colleagues’ activeness and organizational guidelines for using social media form a causal relationship with the use of social media. In addition, respondents’ understanding of their responsibilities affects their use of social media. The more social media is considered as a part of individual responsibilities, the more frequently social media is used. Finally, technological factors must be recognized. The more user-friendly social media tools are considered and the better technical skills respondents have, the more frequently social media is used in the working environment. The central references in relation to knowledge sharing include Chun Wei Choo’s (2006) work Knowing Organization, Ikujiro Nonaka and Hirotaka Takeuchi’s (1995) work The Knowledge Creating Company and Linda Argote’s (1999) work Organizational Learning.

Didactical reconstructions for organizing knowledge in physics teacher education

Physics teachers are in a key position to form the attitudes and conceptions of future generations toward science and technology, as well as to educate future generations of scientists. Therefore, good teacher education is one of the key areas of physics departments education program. This dissertation is a contribution to the research-based development of high quality physics teacher education, designed to meet three central challenges of good teaching. The first challenge relates to the organization of physics content knowledge. The second challenge, connected to the first one, is to understand the role of experiments and models in (re)constructing the content knowledge of physics for purposes of teaching. The third challenge is to provide for pre-service physics teachers opportunities and resources for reflecting on or assessing their knowledge and experience about physics and physics education. This dissertation demonstrates how these challenges can be met when the content knowledge of physics, the relevant epistemological aspects of physics and the pedagogical knowledge of teaching and learning physics are combined. The theoretical part of this dissertation is concerned with designing two didactical reconstructions for purposes of physics teacher education: the didactical reconstruction of processes (DRoP) and the didactical reconstruction of structures (DRoS). This part starts with taking into account the required professional competencies of physics teachers, the pedagogical aspects of teaching and learning, and the benefits of the graphical ways of representing knowledge. Then it continues with the conceptual and philosophical analysis of physics, especially with the analysis of experiments and models role in constructing knowledge. This analysis is condensed in the form of the epistemological reconstruction of knowledge justification. Finally, these two parts are combined in the designing and production of the DRoP and DRoS. The DRoP captures the knowledge formation of physical concepts and laws in concise and simplified form while still retaining authenticity from the processes of how concepts have been formed. The DRoS is used for representing the structural knowledge of physics, the connections between physical concepts, quantities and laws, to varying extents. Both DRoP and DRoS are represented in graphical form by means of flow charts consisting of nodes and directed links connecting the nodes. The empirical part discusses two case studies that show how the three challenges are met through the use of DRoP and DRoS and how the outcomes of teaching solutions based on them are evaluated. The research approach is qualitative; it aims at the in-depth evaluation and understanding about the usefulness of the didactical reconstructions. The data, which were collected from the advanced course for prospective physics teachers during 20012006, consisted of DRoP and DRoS flow charts made by students and student interviews. The first case study discusses how student teachers used DRoP flow charts to understand the process of forming knowledge about the law of electromagnetic induction. The second case study discusses how student teachers learned to understand the development of physical quantities as related to the temperature concept by using DRoS flow charts. In both studies, the attention is focused on the use of DRoP and DRoS to organize knowledge and on the role of experiments and models in this organization process. The results show that students understanding about physics knowledge production improved and their knowledge became more organized and coherent. It is shown that the flow charts and the didactical reconstructions behind them had an important role in gaining these positive learning results. On the basis of the results reported here, the designed learning tools have been adopted as a standard part of the teaching solutions used in the physics teacher education courses in the Department of Physics, University of Helsinki.

When sharing becomes a liability: An intellectual capital approach to describing the dichotomy of knowledge protection versus sharing in intra- and interorganizational relationships

The tension created when companies are collaborating with competitors – sometimes termed co-opetition - has been subject of research within the network approach. As companies are collaborating with competitors, they need to simultaneously share and protect knowledge. The opportunistic behavior and learning intent of the partner may be underestimated, and collaboration may involve significant risks of loss of competitive edge. Contrastingly, the central tenet within the Intellectual Capital approach is that knowledge grows as it flows. The person sharing does not lose the knowledge and therefore knowledge has doubled from a company’s point of view. Value is created through the interplay of knowledge flows between and within three forms of intellectual capital: human, structural and relational capital. These are the points of departure for the research conducted in this thesis. The thesis investigates the tension between collaboration and competition through an Intellectual Capital lens, by identifying the actions taken to share and protect knowledge in interorganizational collaborative relationships. More specifically, it explores the tension in knowledge flows aimed at protecting and sharing knowledge, and their effect on the value creation of a company. It is assumed, that as two companies work closely together, the collaborative relationship becomes intertwined between the two partners and the intellectual capital flows of both companies are affected. The research finds that companies commonly protect knowledge also in close and long-term collaborative relationships. The knowledge flows identified are both collaborative and protective, with the result that they sometimes are counteracting and neutralize each other. The thesis contributes to the intellectual capital approach by expanding the understanding of knowledge protection in interorganizational relationships in three ways. First, departing from the research on co-opetition it shifts the focus from the internal view of the company as a repository of intellectual capital onto the collaborative relationships between competing companies. Second, instead of the traditional collaborative and sharing point of departure, it takes a competitive and protective perspective. Third, it identifies the intellectual capital flows as assets or liabilities depending on their effect on the value creation of the company. The actions taken to protect knowledge in an interorganizational relationship may decrease the value created in the company, which would make them liabilities.

Essays on Managing Knowledge and Work Related Wellbeing

This study explores the relationship between Intellectual Capital and Maintenance of Work Ability. Intellectual Capital is the central framework for analysing the increasing knowledge-intensiveness of business life. It is characteristic of Intellectual Capital that the intersection of human capital, internal structures and external structures is essential. Maintenance of Work Ability, on the other hand, has been the leading paradigm for Finnish occupational health and safety activities since the late 1980s. It is also a holistic approach that emphasises the interdependence of competence, work community, work environment and health as the key to work-related wellbeing. This thesis consists of five essays that scrutinise the focal phenomena both theoretically and empirically. The conceptual model that results from the first research essay provides a general framework for the whole thesis. The case study in the second essay supports a division of intangible assets into generative and commercially exploitable intangibles introduced in the first essay and further into the primary and secondary dimension of generative intangibles. Further scrutiny of the interaction of generative intangible assets in essay three reveals that employees’ wellbeing enhances the readiness to contribute to the knowledge creation process. The fourth essay shows that the MWA framework could benefit knowledge-intensive work but this would require a different approach than has been commonly adopted in Finland. In essay five, deeper analysis of the MWA framework shows that its potential results from comprehensive support of the functioning of an organisation. The general conclusion of this thesis is that organisations must take care of their employees’ wellbeing in order to secure innovativeness that is the key to surviving in today’s competitive business environment.